ArticleHuman molecular genetics2017
Genome-wide association study with additional genetic and post-transcriptional analyses reveals novel regulators of plasma factor XI levels.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
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- Variant-to-Biomarker Pathways in Peripheral Artery Disease: Multiomics Integration and Clinical Translation.Human mutation · 2026Review
- Venous Thrombogenesis and Cervical Cancer: Plasma MicroRNAs as Prognostic Indicators of Tumor Behavior.International journal of molecular sciences · 2025Article
- miR-145 and incident thromboembolism.Blood · 2024Article
- A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment.Journal of thrombosis and haemostasis : JTH · 2024Article
- Genetic Variants Identified by Whole Exome Sequencing in a Large Italian Family with High Plasma Levels of Factor VIII and Von Willebrand Factor.International journal of molecular sciences · 2023Article
- Post-transcriptional control of haemostatic genes: mechanisms and emerging therapeutic concepts in thrombo-inflammatory disorders.Cardiovascular research · 2023Review
- Antithrombin, Protein C, and Protein S: Genome and Transcriptome-Wide Association Studies Identify 7 Novel Loci Regulating Plasma Levels.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism.Nature communications · 2023Article
- Long non-coding RNA crnde promotes deep vein thrombosis by sequestering miR-181a-5p away from thrombogenic Pcyox1l.Thrombosis journal · 2023Article
- Haplotypic variants of COVID-19 related genes are associated with blood pressure and metabolites levels.Journal of medical virology · 2023Article
- Glucokinase regulatory protein: a balancing act between glucose and lipid metabolism in NAFLD.Frontiers in endocrinology · 2023Review
- Article
- Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations.Journal of thrombosis and haemostasis : JTH · 2022Article
- Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus.Nature communications · 2022Article
- Large-scale integration of the plasma proteome with genetics and disease.Nature genetics · 2021Article
- Genetic Profile of Endotoxemia Reveals an Association With Thromboembolism and Stroke.Journal of the American Heart Association · 2021Article
- Association Between Hemostatic Profile and Migraine: A Mendelian Randomization Analysis.Neurology · 2021Article
- Mendelian Randomization Analysis of Hemostatic Factors and Their Contribution to Peripheral Artery Disease-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Genetic association study of fatal pulmonary embolism.International journal of legal medicine · 2021Article
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Authors and funding
27 authors at 12 institutions in 7 countries.
Funding
Abstract
Coagulation factor XI (FXI) has become increasingly interesting for its role in pathogenesis of thrombosis. While elevated plasma levels of FXI have been associated with venous thromboembolism and ischemic stroke, its deficiency is associated with mild bleeding. We aimed to determine novel genetic and post-transcriptional plasma FXI regulators.We performed a genome-wide association study (GWAS) for plasma FXI levels, using novel data imputed to the 1000 Genomes reference panel. Individual GWAS analyses, including a total of 16,169 European individuals from the ARIC, GHS, MARTHA and PROCARDIS studies, were meta-analysed and further replicated in 2,045 individuals from the F5L family, GAIT2 and MEGA studies. Additional association with activated partial thromboplastin time (aPTT) was tested for the top SNPs. In addition, a study on the effect of miRNA on FXI regulation was performed using in silico prediction tools and in vitro luciferase assays.Three loci showed robust, replicating association with circulating FXI levels: KNG1 (rs710446, P-value = 2.07 × 10-302), F11 (rs4253417, P-value = 2.86 × 10-193), and a novel association in GCKR (rs780094, P-value = 3.56 ×10-09), here for the first time implicated in FXI regulation. The two first SNPs (rs710446 and rs4253417) also associated with aPTT. Conditional and haplotype analyses demonstrated a complex association signal, with additional novel SNPs modulating plasma FXI levels in both the F11 and KNG1 loci. Finally, eight miRNAs were predicted to bind F11 mRNA. Over-expression of either miR-145 or miR-181 significantly reduced the luciferase activity in cells transfected with a plasmid containing FXI-3'UTR.These results should open the door to new therapeutic targets for thrombosis prevention.
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